Functional and therapeutic significance of protein kinase D enzymes in invasive breast cancer.

The protein kinase D (PKD) family members, PKD1, PKD2 and PKD3 constitute a family of serine/threonine kinases that are essential regulators of cell migration, proliferation and protein transport. Multiple types of cancers are characterized by aberrant expression of PKD isoforms. In breast cancer PKD isoforms exhibit distinct expression patterns and regulate various oncogenic processes. In highly invasive breast cancer, the leading cause of cancer-associated deaths in females, the loss of PKD1 is thought to promote invasion and metastasis, while PKD2 and upregulated PKD3 have been shown to be positive regulators of proliferation, chemoresistance and metastasis. In this review, we examine the differential expression pattern, mechanisms of regulation and contributions made by each PKD isoform to the development and maintenance of invasive breast cancer. In addition, we discuss the potential therapeutic approaches for targeting PKD in this disease.